When carbon tetrachloride (CC14), bromotrichlormethane (CBrC13), chloroform (CHC13) or carbon tetrabromide (CBr4) were incubated with liver microsomes from phenobarbital pretreated rats in the presence of 2,6-dimethylphenol (DMP), analysis of the reaction mixture by gas chromatography mass spectrometry revealed that 4-chloro-2,6-dimethylphenol (C1DMP) was a metabolite of CC14 and CBr C13, where as 4-bromo-2,6-dimethylphenol (BrDMP) was a metabolite of CBr4. The formation of the metabolites decreased to undetectable levels when the reactions were conducted with heat-denatured microsomes, in the absence of NADPH, or in an atmosphere of N2. These results indicate that the chlorines of CC14 and CBrC13 and the bromines of CBr4 are oxidatively metabolized by rat liver microsomes to reactive and potentially toxic electrophilic metabolites such as C12, HOC1, Br2, or HOBr, that are trapped by DMP to form C1MDP or BrDMP.